Field of the Invention
The present disclosure relates to compositions, kits, uses, systems and methods for treating overweight and obesity using naltrexone plus bupropion, preferably in combination with a comprehensive web-based and/or telephone-based weight management program, and optionally in subjects at increased risk of adverse cardiovascular outcomes.
Description of the Related Art
Obesity has been defined in terms of body mass index (BMI). BMI is calculated as weight (kg)/[height (m)]2. According to the guidelines of the U.S. Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO), for adults over 20 years old, BMI is categorized as follows: below 18.5 is considered underweight, 18.5-24.9 is considered normal, 25.0-29.9 is considered overweight, and 30.0 and above is considered obese (World Health Organization. Physical status: The use and interpretation of anthropometry. Geneva, Switzerland: World Health Organization 1995. WHO Technical Report Series).
The prevalence of obesity has markedly increased over the past three decades, with 32% of men and 36% of women considered obese. These individuals are at increased risk for a variety of chronic conditions associated with obesity, including type 2 diabetes, coronary heart disease, hypertension, stroke, dyslipidemia, gallbladder disease, sleep apnea, certain types of cancer, and osteoarthritis, as well as increased mortality risk from all causes (NHLBI Clinical Guidelines, 1998). Overweight and obesity are also associated with increased all-cause mortality.
Diet and exercise-based behavioral modification is the mainstay of weight management therapy. However, such intervention is often of limited effectiveness and difficult for individuals to adhere to. Therefore, pharmacotherapy has been employed as an adjunct to diet and exercise. Orlistat, lorcaserin, and phentermine/topiramate are currently the only three drugs approved in the United States for the long-term treatment of obesity. A 5-10% weight loss has been determined to lead to significant medical benefits. While orlistat has a favorable safety profile, it can cause loose stools and fecal incontinence, making acceptance by patients difficult. Bariatric surgery (specifically gastric banding) is now indicated for subjects with BMI≥30 kg/m2 who have at least one obesity-related comorbidity. While effective in most cases, it is invasive with possible complications including infection, death, hypoglycemia, failure to lose weight, gastrointestinal symptoms, nutritional deficiencies, depression, sexual and relationship problems, and noncompliance with behavioral recommendations.
U.S. Pat. Nos. 7,375,111 and 7,462,626 disclose the combination of naltrexone and bupropion (NB) for weight loss therapy. Wadden et al. disclose the combination of naltrexone and bupropion as an adjunct to an intensive behavioral modification (BMOD) program for weight loss. Obesity (2011) 19:110-120. The BMOD program described by Wadden et al. was delivered in person to groups of 10-20 persons. Group meetings lasted 90 min and were held weekly for the first 16 weeks, every other week for the next 12 weeks, and monthly thereafter (yielding a total of 28 sessions). Group sessions typically began with a review of participants' eating and activity records and other homework assignments. Group leaders then introduced a new topic in weight control which, during the first 16 weeks, included meal planning, stimulus control, slowing eating, problem solving, social support, and coping with high risk situations. Subsequent sessions covered skills required for maintaining lost weight.
While the combination of naltrexone and bupropion is known to be efficacious for weight management for some patient populations, alone or in combination with an intensive BMOD program, a need exists for an effective treatment of overweight or obesity in subjects at increased risk of adverse cardiovascular outcomes. In addition, there exists a need for a weight management program for use in combination with naltrexone and bupropion that is easier for patients to comply with than existing BMOD programs, but which is still efficacious, particularly in subjects at increased risk of adverse cardiovascular outcomes.